Development of venous silk fibroin artificial vascular grafts using adipose cell-derived stromal vascular fraction

• Project/Area Number: 20K12643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: TANAKA TAKASHI 東京農工大学, 農学部, 産学官連携研究員 (00868200)
• Co-Investigator(Kenkyū-buntansha): 中澤 靖元 東京農工大学, 工学(系)研究科(研究院), 教授 (20456255) ; 朝倉 哲郎 東京農工大学, 工学(系)研究科(研究院), 名誉教授 (30139208) ; 田中 綾 東京農工大学, (連合)農学研究科(研究院), 教授 (70334480)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 間質血管細胞群 / シルクフィブロイン / 人工血管

Outline of Research at the Start

本研究では、シルクフィブロイン(silk fibroin:SF)製人工血管を再生医療における足場材料とし、体内での血管組織の再生を実現することを目的とする。これまで研究してきたSF製人工血管に脂肪組織から脂肪細胞を除いた間質血管細胞群(stromal vascular fraction:SVF)を併行して使用することで、脂肪前駆細胞が有する分化能や増殖因子の分泌能の効果が付与され、血管組織の再生スピードを格段に加速させることが可能になる。そして、SF製人工血管の分解とともに自己血管に置換されることによって、これまで人工血管が不適であった肝胆膵癌の血管再建手術への適応が期待される。

Outline of Final Research Achievements

In this study, it was proved that the artificial vascular grafts made of silk fibroin has a high ability to remodel to self-tissue after implantation for a vein. As remodeling to autologous vessels progresses, they become more resistant to infection, so it was thought that they would be useful as artificial vascular grafts in the hepato-biliary-pancreatic region.
In addition, we collected subcutaneous abdominal fat, liver falciform ligament and peri-ovarian fat for the purpose of evaluating the optimal collection site for the stromal vascular fraction. Peri-ovarian fat contained more stromal vascular fraction than other sites, suggesting higher activity. From this result, it is possible to collect stromal vascular fraction from a more optimal site for the actual implantation of artificial vascular grafts.

Academic Significance and Societal Importance of the Research Achievements

肝がんおよび膵癌などが静脈に浸潤している症例では血管の切除および再建が必要となるケースは多く、その再建には自家静脈や凍結保存静脈が用いられてきたが、代替血管の確保に苦慮している。人工血管は事前の準備を必要とせずに使用できるが、感染や石灰化のリスクが高いため使用が敬遠されている。本研究で作製したシルクフィブロイン人工血管は静脈へ移植後に石灰化を起こすことはなかった。また、移植後に自己血管へとリモデリングする能力を発揮したことからも感染に強い人工血管であることが示された。

Research Products

• [Journal Article] Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications (2022)
  • Author(s): Hussein M. El-Husseiny, Eman A. Mady, Lina Hamabe, Amira Abugomaa, Kazumi Shimada, Tomohiko Yoshida, Takashi Tanaka, Aimi Yokoi, Mohamed Elbadawy, Ryou Tanaka
  • Journal Title: Materials Today Bio Volume: 13 Pages: 100186-100186
  • DOI: 10.1016/j.mtbio.2021.100186
  • Peer Reviewed / Open Access
• [Journal Article] Cultured versus freshly isolated adipose-derived stem cells in improvement of the histopathological outcomes in HCL-induced cystitis in a rat model (2022)
  • Author(s): Hanan Hendawy, Elsayed Metwally, Ahmed Elfadadny, Tomohiko Yoshida, Danfu Ma, Kazumi Shimada, Lina Hamabe, Kenta Sasaki, Ryou Tanaka
  • Journal Title: Biomedicine & Pharmacotherapy Volume: 153 Pages: 113422-113422
  • DOI: 10.1016/j.biopha.2022.113422
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of small-diameter silk vascular grafts implanted in dogs (2021)
  • Author(s): T. Tanaka, R. Tanaka, Y. Ogawa, Y. Takagi, M. Sata, T. Asakura
  • Journal Title: JTCVS Open. Volume: 6 Pages: 148-156
  • DOI: 10.1016/j.xjon.2021.02.008
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of a Water-Dispersed Biodegradable Polyurethane-Silk Composite Sponge Using 13C Solid-State Nuclear Magnetic Resonance as Coating Material for Silk Vascular Grafts with Small Diameters (2021)
  • Author(s): T. Tanaka, Y. Ibe, T. Jono, R. Tanaka, A. Naito, T. Asakura
  • Journal Title: Molecules Volume: 26 Issue: 15 Pages: 4649-4649
  • DOI: 10.3390/molecules26154649
  • Peer Reviewed / Open Access
• [Journal Article] Small-Diameter Artificial Vascular Grafts (2021)
  • Author(s): Tanaka T, Tanaka R
  • Journal Title: Journal of Vascular Medicine & Surgery Volume: 9 Pages: 427-427
  • Peer Reviewed / Open Access
• [Journal Article] Tissue Harvesting Site Effect on the Canine Adipose Stromal Vascular Fraction Quantity and Quality (2021)
  • Author(s): Hanan Hendawy, Akiko Uemura, Danfu Ma, Ryosuke Namiki, Haney Samir, Mahmoud F Ahmed, Ahmed Elfadadny, Hussein M El-Husseiny, Cheng Chieh-Jen, Ryou Tanaka
  • Journal Title: Animals Volume: 11 Issue: 2 Pages: 460-460
  • DOI: 10.3390/ani11020460
  • Peer Reviewed / Open Access
• [Journal Article] Development of Small-Diameter Elastin-Silk Fibroin Vascular Grafts (2021)
  • Author(s): Tanaka T, Abe Y, Cheng CJ, Tanaka R, Naito A, Asakura T.
  • Journal Title: Frontiers in bioengineering and Biotechnology Volume: 8 Pages: 622220-622220
  • DOI: 10.3389/fbioe.2020.622220
  • Peer Reviewed / Open Access
• [Journal Article] Silk fibroin vascular graft: a promising tissue-engineered scaffold material for abdominal venous system replacement (2020)
  • Author(s): S. Kiritani, J. Kaneko, D. Ito, M. Morito, T. Ishizawa, N. Akamatsu, M. Tanaka, T. Iida, T. Tanaka, R. Tanaka, T. Asakura, J. Arita, K. Hasegawa
  • Journal Title: Sci. Rep. Volume: 10 Issue: 1 Pages: 21041-21041
  • DOI: 10.1038/s41598-020-78020-y
  • Peer Reviewed / Open Access